CHUK (Conserved Helix-Loop-Helix Ubiquitous Kinase)
A key regulator of NF-κB signaling and inflammatory responses
Gene Information Card
| Symbol | CHUK |
|---|---|
| Full Name | Component of inhibitor of nuclear factor kappa B kinase complex |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.31 |
| NCBI Gene ID | 1147 ncbi.nlm.nih.gov/gene/1147 |
| Ensembl ID | ENSG00000113368 |
| UniProt ID | O15111 |
| OMIM ID | 600664 |
| HGNC ID | 1974 |
| Aliases | IKK-alpha, IKK1, TCF16, IKBKA |
Description
The CHUK gene encodes the IKK-alpha (IκB kinase alpha) protein, a serine/threonine kinase that forms part of the IKK complex. This complex is essential for activating the NF-κB transcription factor by phosphorylating IκB proteins, leading to their degradation. CHUK plays a critical role in inflammatory responses, immune regulation, cell survival, and development. Mutations in CHUK are associated with immunodeficiency, ectodermal dysplasia, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe combined immunodeficiency with ectodermal dysplasia | Loss-of-function mutations impair NF-κB activation, disrupting immune and skin development | ClinVar, OMIM |
| Incontinentia pigmenti | Hypomorphic CHUK variants cause NF-κB dysregulation, leading to skin and neurological abnormalities | OMIM |
| Breast cancer | CHUK overexpression or amplification promotes NF-κB-driven cell proliferation and survival | COSMIC, NCBI |
| Prostate cancer | Altered CHUK expression contributes to NF-κB-mediated tumor progression | COSMIC |
| Head and neck squamous cell carcinoma | CHUK mutations or copy number changes affect NF-κB signaling and therapy resistance | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 10.2 | Medium |
| Lung | 8.5 | Low |
| Breast | 7.3 | Low |
| Skin | 6.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 12.8 | Medium expression |
| K562 | 10.5 | Medium expression |
| MCF7 | 8.1 | Low expression |
| A549 | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1294C>T (p.Arg432*) | Nonsense | <0.01% | Loss of function; truncation of kinase domain |
| c.1672G>A (p.Glu558Lys) | Missense | <0.01% | Likely loss of function; reduced kinase activity |
| c.1066C>T (p.Arg356Trp) | Missense | <0.01% | Unknown significance; reported in cancer |
| c.1915A>G (p.Ile639Val) | Missense | <0.01% | Unknown significance; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the kinase domain lead to loss of IKK-alpha function, impairing NF-κB activation.
Gain of Function (GOF)
Amplification or overexpression of CHUK in cancers may enhance NF-κB signaling, promoting cell survival and proliferation.
Dominant Negative (DN)
Some missense mutations in the kinase domain may produce a dominant-negative effect by forming inactive IKK complexes.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • I-kappaB kinase activity |
| • NF-kappaB-inducing kinase activity | • ATP binding |
| • signal transduction | • positive regulation of NF-kappaB transcription factor activity |
| • inflammatory response | • apoptotic process |
Pathways
• NF-kappa B signaling pathway
• Toll-like receptor signaling pathway
• TNF signaling pathway
• RIG-I-like receptor signaling pathway
• NOD-like receptor signaling pathway
Protein Summary
CHUK encodes IKK-alpha, a 745-amino acid serine/threonine kinase with an N-terminal kinase domain, a ubiquitin-like domain, and a C-terminal helix-loop-helix domain. It is a core component of the IKK complex, which phosphorylates IκB proteins to activate NF-κB. IKK-alpha also has nuclear functions, including histone phosphorylation and gene regulation. Its activity is tightly regulated by phosphorylation and ubiquitination. Dysregulation of CHUK is implicated in immune deficiencies, developmental disorders, and multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHUK Knockout HEK293 Cell Line | EDJ-KQ556 | Human | 1147 | Details Get a Quote |
| CHUK Knockout A-549 Cell Line | EDJ-KQ18927 | Human | 1147 | Details Get a Quote |
| CHUK Knockout HCT 116 Cell Line | EDJ-KQ18928 | Human | 1147 | Details Get a Quote |
| CHUK Knockout HeLa Cell Line | EDJ-KQ18929 | Human | 1147 | Details Get a Quote |
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